Mammalian cortical neurons will be grown in dissociated cell culture and their physiological properties (including control of resting potential, presence of electrogenic sodium pump, ionic dependence of the action potential and repetitive firing characteristics) will be studied with intracellular microelectrodes. The neurons form extensive excitatory and inhibitory chemical synapses and small circuits. We will study the nature of the transmitters produced, the ionic mechanisms utilized by different transmitters, quantum contents of synapses and the postsynaptic chemosensitivity of the neurons in culture. The system of mammalian cortical neurons in cell cultures will be utilized as a model to study a variety of cellular physiological and pharmacological properties of normal cortex which cannot be studied in the intact animal. Once characterized, the model will be used to study aspects of cortical physiology related to epilepsy. Primary questions to be asked concern: the effects of raised extracellular potassium on cortical neuronal resting membrane potential, spike generation and synaptic function; the effects of presynaptic stimulus modes which mimic the large paroxysmal bursts of spikes seen in neurons in epileptic foci on excitatory, inhibitory and recurrent synapses; and the effects of a powerful anticonvulsant, phenytoin, on normal cortical neuronal function, synaptic function and pathophysiological epileptic phenomena.